We propose to study several aspects of innate defense mechanisms against Candida albicans. We have observed that congenitally thymic deficient (nude) mice are more resistant to a lethal dose of C. albicans than are their phenotypically normal littermates (NLM). Because most of the NLM die within 3-5 days after injection of the fungus (whereas nudes survive past 14 days), we believe the differences are due to innate defense mechanisms rather than specifically acquired immunity. The susceptibility of nudes reconstituted with a thymus will be examined to determine if the differences are thymic dependent. To rule out the possibility that the differences in susceptibility are dependent upon acquired immunity, we will use, in addition to nude mice, mice deficient in acquired hormonal immunity (anti-u-treated mice), and mice having a combined immunodeficiency (anti-u-treated nude mice). By treating nudes and NLM with either anti-neutrophil or anti-macrophage serum, or with silica, the effect of selective depletion of neutrophils or macrophages on resistance to C. albicans will be studied. Using a new in vitro chemotaxis test devised by us, we have demonstrated that phagocytic cells may be attracted to an area of candida activity by chemotactic factors released by the fungus. The chemotactically active materials will be isolated and characterized from C. albicans grown in vitro. The activities of the factors will be tested against both neutrophils and macrophages from the various types of mice as described below. Candidiasis is a major nosocomial disease and we believe our studies will lead to a greater understanding of mechanisms which render an individual resistant to the disease.